[3+2] Cycloaddition Reaction for the Stereoselective Synthesis of a New Spirooxindole Compound Grafted Imidazo[2,1-b]thiazole Scaffold: Crystal Structure and Computational Study

Abstract

A new spirooxindole hybrid engrafted imidazo[2,1-b]thiazole core structure was designed and achieved via [3+2] cycloaddition reaction approach. One multi-component reaction between the ethylene derivative based imidazo[2,1-b]thiazole scaffold with 6-Cl-isatin and the secondary amine under heat conditions afforded the desired compound in a stereoselective manner. The relative absolute configuration was assigned based on single-crystal X-ray diffraction analysis. Hirshfeld calculations for 4 revealed the importance of the H…H (36.8%), H…C (22.9%), Cl…H (10.4%) and S…H (6.6%), as well as the O…H (4.7%), N…H (5.3%), Cl…C (1.6%), Cl…O (1.0%) and N…O (0.5%) contacts in the crystal stability. DFT calculations showed excellent straight-line correlations (R2 = 0.9776–0.9962) between the calculated and experimental geometric parameters. The compound has polar nature (3.1664 Debye). TD-DFT and GIAO calculations were used to assign and correlate the experimental UV-Vis and NMR spectra, respectively.

Stereoselective Synthesis of a Novel Series of Dispiro-oxindolopyrrolizidines Embodying Thiazolo[3,2-a]benzimidazole Motif: A Molecular Electron Density Theory Study of the Mechanism of the [3 + 2] Cycloaddition Reaction

“…Barakat et al are engaged in a research program to develop a new set of compounds based on spiro-heterocycles. In a recent study they constructed a new spirooxindole compound including a thiazolo [3,2-a] benzimidazole pharmacophore and studied its chemical reactivity (Compound X, Figure 1) [15]. Due to the variety of spiro-compounds, in particular spriooxindoles, they have a wide range of biological targets including anti-cancer, anti-inflammatory, diabetes, and others [16][17][18][19][20].…”

“…Based on the above findings, the aim of the present work was to prepare and study several new spiro-compounds based on thiazolo [3,2-a] benzimidazole via the [3 + 2] cycloaddition (32CA) reaction approach [15]. This procedure involves a one-pot multi-component synthesis that enables the formation of a diversity of highly complex molecules through an efficient, straightforward, and selective transformation.…”

“…Many protein Kinase inhibitors for anti-cancer treatment have been designed and reported based on the annulation of the benzimidazole scaffold and between these targets' aurora kinase, CK2, CDK, FGFR, EGFR, and VEGFR-2[14], in order to explore the chemistry of this interesting scaffold which has gained a lot of attention from chemists.Barakat et al are engaged in a research program to develop a new set of compounds based on spiro-heterocycles. In a recent study they constructed a new spirooxindole compound including a thiazolo[3,2-a] benzimidazole pharmacophore and studied its chemical reactivity (Compound X, Figure1)[15]. Due to the variety of spiro-compounds, in particular spriooxindoles, they have a wide range of biological targets including anti-cancer, anti-inflammatory, diabetes, and others[16][17][18][19][20].…”

Synthesis and SARs study of novel spiro‐oxindoles as potent antiproliferative agents with CDK‐2 inhibitory activities

“…Recently, Barakat et al conducted a thorough study of this spirooxindole scaffold and have so far published several articles with an emphasis on drug discovery research focused on the anticancer reactivity of these scaffolds. [ 47–63 ]…”